Human Papillomavirus E6 - host cell receptor, GRP78, binding site prediction.

Human Papillomavirus (HPV) is the main cervical cancer-promoting element that transmitted through sexual routes. Anal, head, and throat cancers were also reported to be accompanied by HPV infection. E6 is one of the HPV non-structural proteins which is responsible for cell differentiation by targeting tumor suppressor genes p105Rb and p53. E6 was reported to be stabilized by two chaperone proteins; Glucose Regulated Protein 78 (GRP78) and Heat Shock Protein 90 (HSP90). GRP78 is responsible for the unfolded protein response of the cells, and it was reported to be upregulated in many cancers, including cervical cancer. It was reported that knocking out GRP78 destabilize E6 leading to faster degradation of E6 in vivo. The current work predicts the possible binding mode between E6 and GRP78 based on sequence and structural similarities. Importance: Understanding the binding behavior of GRP78 can pave the way for drugs that can prevent this interaction between the host cell proteins and the viral protein E6 that crucial for cancer propagation. Once GRP78 binding is inhibited, E6 will be destabilized and prone to a faster degradation rate by the host cell degradation machinery. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.